SAMHD1: Recurring roles in cell cycle, viral restriction, cancer, and innate immunity

Abstract

Sterile alpha motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) is a deoxynucleotide triphosphate (dNTP) hydrolase that plays an important role in the homeostatic balance of cellular dNTPs. Its emerging role as an effector of innate immunity is affirmed by mutations in the SAMHD1 gene that cause the severe autoimmune disease, Aicardi–Goutieres syndrome (AGS) and that are linked to cancer. Additionally, SAMHD1 functions as a restriction factor for retroviruses, such as HIV. Here, we review the current biochemical and biological properties of the enzyme including its structure, activity, and regulation by post-translational modifications in the context of its cellular function. We outline open questions regarding the biology of SAMHD1 whose answers will be important for understanding its function as a regulator of cell cycle progression, genomic integrity, and in autoimmunity.

Keywords:

• SAMHD1
• dNTP metabolism
• nucleotide
• autoimmune disease
• Aicardi–Goutieres syndrome
• HIV

Disclosure statement

The authors declare no competing or conflicting interests.

Additional information

Funding

This work has been supported through funding by NIH RO1 GM108827 (TH) and T32 GM095440 support (CHM), and the Comprehensive Cancer Center of Wake Forest University National Cancer Institute Cancer Center Support Grant P30CA012197.